From: Joao Pedro de Magalhaes (joao.magalhaes@fundp.ac.be)
Date: Thu Jan 17 2002 - 07:22:33 MST
Hi!
You wrote:
>> A recent article in the journal Nature reported mice that had a
>> mutation that reduced cancer but also substantially (20%) reduced
>> their lifespan.
>
>Duane -- don't you mean "increased" their lifespan?
>If you don't cite specific sources it is difficult to verify
>the message.
Duane probably means this paper:
Tyner et al. (2002). "p53 mutant mice that display early ageing-associated
phenotypes." Nature 415(6867):45-53.
If he does, then it's reduced life span. What was relevant was that
alongside the reduced life span were several signs of accelerated aging. If
you remember the p66 KO mice that lived longer you think how everything
makes sense. p53 increases apoptosis and when you increase p53 -- as
indirectly happens in this paper --, you get faster aging mice. When you
disrupt p66 -- also involved in apoptotic pathways, although no one knows
exactly how --, you get delayed aging and increased life span. I should
point that when you work with mice -- I don't but I heard about it --, you
notice that genomic misregulation is high, apoptosis is very high too and,
presumably, this is a burden for the metabolism. So, it makes some sense
that less apoptosis means higher longevity and vice-sersa. Finally, if you
don't know, knocking out p53 produces mice with very high cancer rates that
die quickly -- due to cancer, of course. (Presumably shows that there is a
threshold on how much you can lower apoptosis.)
>> This gives further evidence that a fine balance needs
>> to be maintained between these two processes for any serious attempts
>> at life extension.
>
>This is (at least to me) obvious. Mammals started out as very small
>creatures. As they get larger there is an increasing need to be able
>to deal with cancer (which is a defective program of a single cell).
>Humans have a very good anti-cancer program but it is much less
>capable than that which must exist in elephants and whales.
True but it doesn't mean cancer and aging are related. Remember that mice
have lots of cancer and lots of genetic misregulation events but the same
doesn't happen in humans.
>Obviously the genetic program degrades over time -- because there
>are insufficient resources dedicated to preserving the genetic
>program in a "pristine" state. We have to wrestle with not only
>the fact that the genetic program was not designed to maintain
>human bodies for 100+ years but that it is becoming corrupted
>during that period. We must solve *both* problems.
Probably true from a statistical point of view. Yet even in very old
individuals I'm sure you can find perfectly preserved genomes in some cells
-- only these will probably be a lower proportion. You could also rephraze
that sentence: "We have to wrestle with not only the fact that the genetic
program was not designed to maintain human bodies 100+ but that it isn't
designed to maintain itself 100+ years."
Best wishes.
---
Joao Pedro de Magalhaes
The University of Namur (FUNDP)
Unit of Cellular Biochemistry & Biology (URBC)
Rue de Bruxelles, 61. B-5000 Namur. Belgium.
Fax: + 32 81 724135
Phone: + 32 81 724133
Reason's Triumph: http://users.compaqnet.be/jpnitya/
New website on Aging: http://www.senescence.info
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